Factors obtained from yeast cells have been found to support a variety of effector activities. For example, one or more yeast factors stimulate the growth of other yeast cultures; one or more yeast factors stimulate the respiration of yeast cells; one or more yeast factors stimulate oxygen uptake in yeast, cultured fibroblasts, rat liver and rat abdominal skin; one or more yeast factors stimulate wound healing by the formation of collagen and new granulation tissue and the rate of epithelialization in rabbit ear wounds; and one or more yeast factors stimulate angiogenesis.
A crude extract containing one or more of said factors is obtainable by alcohol extraction of live yeast cells. The derivative obtained therefrom is a dark brown viscous fluid. The extract is commonly referred to as live yeast cell derivative.
Sperti, in U.S. Pat. No. 2,320,478, disclosed an alcoholic extract of yeast that was said to stimulate skin respiration. The active material was said to be substantially free of protein.
Mazarin, in U.S. Pat. No. 4,575,457, used a yeast extract obtained according to Sperti (supra) in a toothpaste which was claimed to be useful for improving the healing rate of gingivitis.
An alcoholic extract of yeast is a component of an over-the-counter preparation for treating hemorrhoids.
Kaplan (Arch. Surg. 119:1005-1008, 1984) stated that an alcoholic extract of yeast cells, prepared essentially as taught in Sperti (supra) appeared to enhance angiogenesis and epithelialization when applied as an ointment to wound sites.
Bentley et al. (Arch. Surg. 125:641-646, 1990) alleged to have obtained a low molecular weight mixture of peptides ranging in size from 6,000 to 17,000 daltons that showed angiogenic activity and stimulated wound healing. A crude alcoholic extract was centrifuged to remove cellular debris and the clarified supernatant was applied to a preparative gel filtration column. The resulting filtrate was analyzed by gel filtration, polyacrylamide electrophoresis and ion exchange chromatography.
Angiogenic activity was limited to low molecular weight peptides. Chemical analysis revealed that the extract contained a glucose disaccharide in which the glucose molecules are linked to each other by a 1.fwdarw.1 bond. Trehalose, a disaccharide which is abundant in yeast, is characterized by just such a bonding relationship.
In bioassays, the low molecular weight peptides were asserted to exhibit wound healing activity, however the concentration of peptides required to effect a biologic response were orders of magnitude greater than those required of other growth factors known in the art. Thus Bentley et al. concluded that the yeast derived peptides are not classic growth factors that act through cell surface receptors and a tyrosine kinase mechanism.
It is within this framework that the studies to be described hereinbelow were instigated. High molecular weight yeast derived factors were obtained in substantially pure form and said factors showed significant mitogenic activity.